Background Recent studies have shown that the extent of extravalvular (extra-aortic valve) cardiac damage in patients with severe aortic stenosis (AS) have important prognostic implications for clinical outcomes after aortic valve replacement (AVR). Aims The aim of the present study is to evaluate the prognostic impact of a defined staging classification (“Généreux Staging Classification”) (GSC) characterizing the extent of extravalvular cardiac damage in patients with severe AS undergoing percutaneous transcatheter aortic valve implantation (TAVI). Methods A total of 102 consecutive patients, admitted in our institution between 2011–2017, with severe AS (echo-defined by peak aortic velocity, mean transvalvular gradient or aortic valve area) and symptoms related to AS (dyspnea, heart failure, angina or syncope) undergoing TAVI, were included. These patients were pooled and classified according to the presence or absence of cardiac damage as detected by echocardiography prior to TAVI, regarding the GSC: no extravalvular cardiac damage (Stage 0), left ventricular damage (Stage 1), left atrial or mitral valve damage (Stage 2), pulmonary vasculature or tricuspid valve damage (Stage 3), or right ventricular damage (Stage 4). Two-year outcomes were compared using Kaplan– Meier techniques and multivariable Cox proportional hazards models were used to identify 2-year predictors of mortality. Results Out of 102 patients, 57 were male (55.9%). Mean age was 83.46±4.23 years. 2 patients (2.1%) were classified as Stage 0; 20 patients (20.3%) as Stage 1; 55 patients (54.2%) as Stage 2; 22 (21.6%) as Stage 3; and 3 patients (2.9%) as Stage 4. Two-year mortality was 0.0% in Stage 0, 5.0% in Stage 1, 5.5% in Stage 2, and 44.0% in Stages 3–4. After multivariable and univariate analysis, stage of cardiac damage was independently associated as predictor for all-cause mortality at 2-years, after TAVI (HR 2.8 [1.3±6.2], p<0.01). There were not another identificable predictors of 2-years death (age, sex, hypertension [78.5% of total patients], dislipemia [64.7%], diabetes [30.3%], smoking [78.5%], O2-chronic obstructive pulmonary disease [27.5% of total patients], renal insufficiency [78.5%], previous coronary artery disease [37.3%], peak aortic velocity, mean transvalvular gradient, and aortic valve area). Conclusions Given the strong association demonstrated in this study between advanced staging of cardiac damage and worse clinical outcomes after TAVI in short-middle term survival, consideration of the GSC in patients with severe AS in future recommendations for risk stratification might be useful. Two-year all-cause death in TAVI by GSC. Funding Acknowledgement Type of funding source: None

Funding Acknowledgements Type of funding sources: None. INTRODUCTION After publication of the 2019 ESC Guidelines for dyslipidemia, the LDL cholesterol target in patients with very high cardiovascular risk was reduced from 70 mg/dl to 55 mg/dl. Currently, there is more and more evidence that getting these levels is very important in prognosis, to avoid new cardiovascular events. The paradigm of this situation could be represented by young patients after STEMI, in which secondary prevention is essential to achieve a long-life expectancy. OBJECTIVE The aim of the present study is to analyze the impact the new guidelines have had on the control of LDL cholesterol in a population of young patients after STEMI, one year after their publication. METHODS A total of 101 consecutive young patients (aged ≤ 40 years) presenting with STEMI admitted at our center between 2006 and 2017 were included. There were no exclusion criteria. We collect demographic, clinical and treatment information, and laboratory values in september/2019 and again one year later.  RESULTS Out of 101 patients, 89 were male (88.1%). Mean age was 35.87 ± 4.07 years. Among the classic cardiovascular risk factors, dyslipidemia (44.5%) was the second one most prevalent in our cohort, after smoking (93.1%). In September/2019, only 66.3% of our patients had a recent LDL-cholesterol control, and only 20.9% of them had a target LDL-cholesterol lower than 55 mg/dl ("LDL-c -goal"). During the following year, a new determination of LDL cholesterol was only carried out in 18 patients out of the total sample, with these results: 15 patients had an LDL> 55 mg/dl; 2 patients maintained an "LDL-c-goal", and only a single patient achieved optimal control (from 81 mg/dl to 39 mg/dl) coinciding with the change from low to high intensity statin. Regarding lipid-lowering treatment, in September/2019 the 87.7% of our population were taking statins, 21.9% ezetimibe, and 0.0% PCSK9-inhibitors. In that moment, in 6 patients, the lipid-lowering treatment was reduced (all of them had LDL values were between 65-105 mg/dl). One year later, in September/2020, 82.2% were taking statins, 21.9% ezetimibe, and in 1 patient was started with the PCSK-9 inhibitor. Thirteen patients (12.9%) had suffered a reinfarction during follow-up, but none in the last year. CONCLUSIONS Despite of the new LDL-cholesterol target established by the ESC Guidelines, we have not improved our lipid control in a population with high cardiovascular risk -with a percentage of cardiovascular events during mean follow-up that is not negligible-, being only 1 of each 5 patients correctly treated. We must carry out a closer clinical and analytical follow-up, by increasing our efforts in secondary prevention, and perhaps the Cardiac Rehabilitation Units can play an essential role in this objective. It is possible that the Covid-19 pandemic could have influenced these results. Abstract Figure. Lipid-lowering treatment.

Funding Acknowledgements Type of funding sources: None. Introduction The transcatheter aortic valve implantation (TAVI) it´s an alternative to surgery in patients with low, moderate and high risk. The indexed systolic volume (ISV) is a parameter that has been associated with adverse events in this scenario. However, there are conflicting reports. The aim of this study was to evaluate the impact of the ISV in patients with severe aortic stenosis in which TAVI was performed. Methods Observational, retrospective and single institution study of patients in which a TAVI was performed between 2010 and 2020. The baseline characteristics of the patients were recorded and then the data were analyzed in two cohorts depending on the presence or not of an increase 3.5 ml/m2 of the ISV after TAVI in relation to the baseline (cohort A and cohort B). The cut-off point of 3.5 ml/m2 was chosen due to the fact that it was the median of the difference in the ISV before and after the TAVI. Results A total of 131 patients were included with a mean age of 84 years old (81-86). 74 patients (56.5%) presented an increase 3.5 ml/m2 of the ISV after TAVI, while there was an increment less than 3.5 ml/m2 in 57 patients (43.5%). The cohort A patients were older and had less prevalence of high blood pressure (Picture 1). Differences in survival weren´t found between the two cohorts, neither in the patients that before the TAVI had an ISV <3.5ml/m2 in relation to those with an ISV 3.5 ml/m2. Conclusions In our population, an increase of the ISV after TAVI wasn´t associated with less adverse events in the follow up. The survival was similar between the patients that before the TAVI had an ISV <3.5ml/m2 and those with an incremented ISV. Prospective studies with bigger cohorts are needed in order to prove these results. Abstract Figure. Baseline Characteristics and Events  Abstract Figure. Kaplan Meier Graphics

Background Malignancy is one of the leading causes of mortality in the long term follow up after heart transplantation (HT). Male sex has been described as an independent risk factor for developing cancer in this group of patients. However, the real incidence of all type of neoplasm and its impact prognosis in mortality in both group of sex remains unknown. Purpose The aim of this study was to assess the incidence of malignancy and the disparity in its relative weight as a cause of death between genders. Methods Observational longitudinal study of heart transplant patients from the Spanish post-HT Tumor registry (SPHTTR) who underwent HT in this country from 1984 to 2017. Re-transplant, combined transplant patients and those with survival less than 3 months since HT were excluded. Incidence and mortality rates per 1000 person-year for all tumors, skin cancer (including melanoma), lymphoma and non-skin solid malignancy (NSSM) were calculated for both groups of sex. The main end-point of the study was death for any causes related to cancer following HT. Survival curves since first diagnosis of neoplasia were constructed using Kaplan Meier estimates and comparisons among genders were performed using long-rank test. Results A total of 5865 patients (81.6% male, 18.4% female) were included in the analysis. Incidence and mortality rates in both genders are summarized in Table 1. Total cumulative incidence rate of all tumors, non-skin solid malignancy and lung cancer were higher in men patients (All tumors: 44.8 vs 25.7 per 1000 person-year; female to male RR 0.68, 95% CI 0.60–0.78, p<0.001). Mortality rates were also higher in male patients for all types of tumors (RR 0.76, CI 95% 0.62–0.94, p=0.01) and for NSSM (RR 0.60, 95% CI 0.44–0.80, p=0.001) albeit not for cutaneous neoplasia or lymphoma. Survival curves are shown in figure 1 and display significant differences among both genders (p=0.0037). Table 1 Type of tumor Female Male Female to Male Incidence RR Female to male mortality RR Incidence rate* Mortality rate* Incidence rate* Mortality rate* RR p-value RR p-value All tumors 25.7 (22.8–29.0) 94.0 (77.3–114.3) 44.8 (42.9–46.8) 129.6 (120.9–138.9) 0.68 (0.60–0.78) <0.001 0.76 (0.62–0.94) 0.01 Skin cancer 12.6 (10.6–15.0 63.2 (45.4–88.0) 24.4 (23.0–25.9) 70.4 (62.6–79.1) 0.62 (0.52–0.74) <0.001 0.88 (0.62–1.25) 0.481 Lymphoma 2.0 (1.3–3.0) 137.8 (80.0–237.3) 2.5 (2.1–3.0) 237.5 (187.9–300.2) 0.84 (0.52–1.36) 0.483 0.58 (0.32–1.06) 0.076 NSSM 11.1 (9.3–13.4) 125.0 (95.2–164.0) 17.5 (16.4–18.8) 234.7 (214.0–257.5) 0.75 (0.62–0.92) <0.001 0.60 (0.44–0.80 0.001 NSSM: Non-skin solid malignancy. *Per 1000 person-year. Figure 1 Conclusions Incidence of malignancy post-HT is higher in men than in women specially for skin cancer and de novo solid tumors. The relative weight of cancer as a cause of death was also higher in men than in women, furthermore, this could have impact prognosis in HT survivors.

Background: Cytoplasmatic expression of Aldehyde dehydrogenase 1 A1 (ALDH1A1) has been identified as a cancer stem cell marker and related to an unfavorable prognosis. However, nuclear expression of ALDH1A1 has not been described in breast cancer (BC) patients yet. Methods: A retrospective, historical cohort study of patients diagnosed with early or locally advanced triple negative (TN) and human epidermal growth factor receptor 2 positive (HER2+) BC treated with neoadjuvant chemotherapy was conducted. Patients who had an available tumor sample from the diagnosis and who underwent surgery after the neoadjuvant treatment were included. Metastatic patients and non-evaluative biopsy sample cases were excluded. Immunostaining against ALDH1A1 was performed. The aim of this study was to assess the expression of nuclear ALDH1A1 in BC and its relation with clinicopathological features and outcomes.Results: 75 patients were analyzed (100% women, mean age 53.6±11.7 years, 42.7% TN, 57.3% HER2+ tumors). 28% had obesity, 32 (42.7%) had a tumor size ≤5 cm and 52 (69.3%) positive lymph nodes. 40 (53.3%) patients had cytoplasmatic ALDH1A1 expression. From them, 18 (24%) also expressed nuclear ALDH1A1 staining and 22 (29.3%) only had cytoplasmatic expression. 57 (76%) patients had negative nuclear ALDH1A1. At the end of the follow-up (54.4 [38.3-87.6] months), 47 patients (62.7%) remained disease free and 20 (26.7%) died. Patients with nuclear ALDH1A1 had higher prevalence of obesity when comparing to exclusively positive cytoplasmatic ALDH1A1 (p = 0.003) and versus those with negative ALDH1A1 expression (p = 0.017); and also, smaller size compared to those without nuclear ALDH1A1 staining (p = 0.044). Furthermore, in patients with positive nuclear ALDH1A1 a tendency to superior disease-free survival (DFS) and overall survival (OS) was observed when compared to positive cytoplasmatic and negative ALDH1A1 tumors, albeit not statistically significant. Conclusions: In this cohort, nuclear positive expression of ALDH1A1 was higher in patients with obesity and smaller tumors. Patients with positive nuclear ALDH1A1 carcinomas appear to have better DFS and OS, although this was not statistically significant. Further research studies are needed to understand the functions of this enzyme and its possible role as a predictive and prognostic marker in BC.